This study was designed to evaluate the association between family structure and the initiation of illicit drug use among a representative sample of 12-17 year old adolescents. The hypothesis was that adolescents who do not live with either their mother or father might are at an increased risk for starting illicit drug use. This hypothesis was tested using an incident case-control analyses of self-report data from the 1992 National Household Survey on Drug Abuse. A post-stratification procedure was used to hold constant shared neighborhood characteristics. Multiple logistic regression models were used to estimate relative risk of initiating illicit drug use among adolescents residing in homes with varying kinds of parents present, holding constant age, sex, ethnicity, family income, and number of siblings. A total of 433 incident cases and 1830 neighborhood-matched controls were identified. The risk of starting illicit drug use was highest for father alone families, followed by mother/stepfather families, no-parent families and lowest for mother/father families. Mother alone and father/stepmother families did not show any significantly higher risk than mother/father families.